A recent study in a population of Chinese women revealed an association between inheritance of a moderately common polymorphism (0.10-0.15) of HER2 (I655V) and excess risk of breast cancer (OR = 12.7, 95% CI = 1.6-99.5) (Xie et al., J. Natl. Cancer Inst., 92:412-417, 2000). Also, a stronger relationship was claimed in younger women (adjusted OR = 1.7, 95% CI = 1.1-2.6). We tested this hypothesis in a population of US women enrolled in a hospital based case control study in New York City (n = 137 cases and 291 controls, matched 1:2 on age and self-reported race/ethnicity). No evidence was found to support an association between inheritance of the 655-valine variant of HER2 and excess breast cancer risk. Our population consisted of African-Americans (n = 34 cases/58 controls), Caucasians (n = 77/162) and Latinas (26/71). Genotypic distributions for all groups were consistent with Hardy-Weinburg population laws (all p-valves fell within the range 0.16-0.91). Interestingly, HER2V655 allelic frequencies were found to vary with race (African-Americans 0.05, Caucasians 0.16, Latinas 0.15), differences between African-Americans and Caucasians and African-Americans and Latinas were significant (p-values = 0.002 and 0.001, respectively). No association was found between inheritance of HER2V655 and breast cancer, either in the group as a whole (carriers OR = 1.2, 0.8-1.9 or homozygotes OR = 1.2, 0.4-4.2) or when considered by racial groups or when limited to younger women (<54 years:carriers OR = 1.4, 0.7-2.6 or homozygotes OR = 3.1, 0.7-14.3).
Health Effects Laboratory Division, NIOSH, 1095 Willowdale Road, Morgantown, WV 26505, USA